Oxidative Stress in Obstructive Sleep Apnea Syndrome: Comparison
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Please note this is a comparison between Version 2 by Jessie Wu and Version 1 by Christian Barbato.

Obstructive sleep apnea syndrome (OSAS) is a disease that affects 2% of men and 4% of women of middle age. It is a major health public problem because untreated OSAS could lead to cardiovascular, metabolic, and cerebrovascular complications.

  • OSAS
  • oxidative stress
  • hearing
  • auditory
  • biomarker
  • otorhinolaryngology

1. Introduction

Obstructive sleep apnea syndrome (OSAS) is a respiratory disease relating to sleep. It is characterized by five or more respiratory events (apnea, hypopnea, or RERA), with a specific symptomatology. Every episode of apnea or hypopnea persists for at least 10 s, is associated with a loss of blood oxygenation of 3–4%, and ends with a short and unconscious awakening from sleep. A population of 2% of women and 4% of men older than 50 years old is often affected by this pathology [1]. Car accidents and cardiovascular morbidity and mortality are the main consequences of untreated OSAS. The pathology is exacerbated by alcohol consumption, sedative use, and weight gain. Obesity is one of the main risk factors for OSAS [2]. In adults, multiple craniofacial anomalies are associated with OSAS, including the increased distance of the hyoid bone from the mandibular plane, decreased mandibular and maxillary projection, a downward and posterior rotation of mandibular and maxillary growth, increased vertical facial length, increased vertical length of the posterior airway, and increased cervical angulation [3]. OSAS is classified as an apnea hypopnea index (AHI) of 5–15 indicating mild OSAS, 15–30 moderate OSAS, and more than 30 severe OSAS [4]. The etiology and the mechanism of the collapse of the upper airway are multifactorial, even though the main feature is the interaction between the propensity of the upper airways to collapse and the distension of the dilator’s pharyngeal muscles. Furthermore, the reflex pathway from the central nervous system to the pharynx can fail in maintaining the patency of the upper airway [5]. The three main obstruction areas are nose, palate, and hypopharynx. The most common OSAS symptoms are snoring, restless sleep, and daytime sleepiness. Sleepiness and fatigue might be exacerbated by multiple other medical conditions that should be considered in a patient suspected of OSAS. With the increasing prevalence of OSAS in patients affected by cardiovascular diseases, cerebrovascular accidents, and diabetes mellitus, these populations should be carefully evaluated for signs and symptoms of OSAS [6]. Physical examination helps to reach the diagnosis, and it includes BMI calculation, blood pressure, neck circumference, body habitus, mandible and maxilla position, facial anomalies, nose and paranasal sinuses evaluation, tongue position and size, elongation of palate and uvula, tonsil size, Mallampati score, dentition, Hyoid, and mandible position, including retrognathia. Nasal and laryngeal endoscopy is important for the evaluation of the upper airways [7]. The Muller maneuver is performed with an awake patient, which produces a negative pressure inhaling against a closed glottis, with a closed mouth and nose, to induce a collapse of the upper airways. To evaluate better the sites of obstruction in OSAS patients, Drug-Induced Sleep Endoscopy (DISE) is the gold standard to guide the physician to the best therapeutic option [8]. DISE is performed with a fiberoptic nasopharyngoscopy to evaluate the region of the respiratory collapse, during a drug-induced sleep [9]. To standardize the findings during DISE, VOTE classification (Velum, Oropharynx, Tongue base, Epiglottis) is a more reliable tool to predict surgery outcomes [10]. Nocturnal PSG is the gold standard for the diagnosis. OSAS treatment should be approached gradually. Weight loss should be recommended to all OSAS patients that are overweight. CPAP is the gold standard for the treatment of moderate and severe OSAS. [11]. Multiple studies have demonstrated its efficacy in reducing the AHI index, improving sleeping and quality of life in general, and reducing the risk of cardiovascular morbidity and car accidents. Oral applications are recommended in patients with mild and moderate OSAS and, in some cases, in patients who cannot tolerate the CPAP [12,13][12][13]. Regarding surgery, the site of obstruction should be identified in every patient to address the type and the extent of the surgical procedure [14]. Septoplasty, turbinate reduction, nasal valve surgery, and sinus surgery are procedures with the purpose of treating the nasal obstruction associated with OSAS [15]. However, this type of surgery alone does not significantly improve the disease. Improving nasal patency is helpful in the recovery of physiological breathing and tolerating CPAP [16]. Uvulopalatopharyngoplasty (UPPP) associated with bilateral tonsillectomy, by resection of redundant mucosa and pharyngeal tissue, has been developed to treat palatal obstruction [17]. This procedure should be limited to patients with oropharyngeal obstruction. Lateral pharyngoplasty was described for the first time in 2003 as an alternative to UPPP [18]. This restudyearch showed a significant decrease in the AHI index associated with an improvement in the quality of sleep and daytime sleepiness. Barbed pharyngoplasty demonstrates effectiveness and safeness with a significant improvement in the patient’s symptoms and AHI [19,20][19][20]. Partial midline glossectomy, lingual plasty, and radiofrequency ablation of the tongue base have been developed to treat retro-lingual collapse. Lingual tonsillectomy could be useful in patients affected by lingual tonsillar hypertrophy. In selected cases, lingual tonsillectomy, reduction in the aryepiglottic folds, and partial epiglottectomy could be performed [21]. However, because of the significant incidence of postoperative edema, these procedures are often executed in combination with a tracheotomy to protect the upper airway. Other surgical treatments are genioglossal advancement and hyoid advancement, which have the aim to enlarge the retro lingual space. Transoral robotic surgery (TORS) has been shown to be effective and safe [22]. Untreated OSAS could lead to cardiovascular, metabolic, and cerebrovascular comorbidity. The pathophysiology of these complications is not entirely elucidated but seems to involve multiple pathways, one of which is endothelial damage due to oxidative stress. This is defined as an imbalance between the pro-oxidant and antioxidant system, which leads to the excessive formation of reactive oxygen species (ROS). ROS and oxidative stress are tightly associated with hypoxia in OSAS patients [23,24][23][24]. Oxidative stress is one of the most important features in the development of cardiovascular comorbidity. Oxidative stress and intermittent hypoxia could lead to multiorgan impairment. One of these organs susceptible to oxidative stress is the auditory system. The cochlear hair cells are most vulnerable to oxidative stress, particularly those located at the base of the cochlea itself, leading to sensorineural hearing loss (SNHL), especially for high frequencies, in response to multiple causes, such as ototoxic agents, noise exposure, and aging. Antioxidant therapy is promising, suggesting the need to discover new biomarkers for an early diagnostic framework of OSAS patients [25]. Antioxidant therapy has also proven to be effective for acquired disorders that induce SNHL [26].

2. The Role of Antioxidant Therapy

Antioxidants are molecules that inhibit ROS production and regulate oxidative stress. They can be endogenous, produced in vivo, and exogenous, taken from the outside. Endogenous antioxidants are the molecules wresearchers discussed early in this section. Exogenous antioxidants comprehend water and lipid-soluble molecules. Water-soluble antioxidants are methionine, vitamin C, carnitine, riboflavin, niacin, folic acid, polyphenols, and catechins. Methionine has the function to reduce cholesterol blood levels and to remove ROS [92][27]. Riboflavin and niacin eliminate lipid peroxides, with the aid of the GSH [93][28]. Vitamin C reduces toxicity by removing hydroxyl radicals [94][29]. Folic acid lowers homocysteine levels [95][30]. Lipid soluble antioxidants are β-carotene, vitamin E, astaxanthin, and coenzyme q10. Vitamin E gives stability to the biological membranes. Coenzyme q10 lowers the levels of vitamin E radicals after ROS removal [96][31]. There are some antioxidants that are both water and fat soluble, like Gingko Biloba and alpha lipoic acid. The latter has both antioxidant properties and restores the antioxidant ability of glutathione, vitamin A, vitamin E, and vitamin C [97][32]. It has been demonstrated that vitamins C and E are potential treatments of SNHL. In fact, it seems that vitamins improve hearing function in patients with sudden hearing loss [98][33]. It has been found, in an animal study, that vitamin E protects hair cells from the ototoxic damage of the cisplatin [99][34]. For what concerns OSAS patients, it has been shown that vitamin C and N-acetylcysteine reduce oxidative stress [58][35]. N-acetylcysteine reduces oxidative stress in OSAS patients by reducing peroxidized lipids and increasing glutathione. Furthermore, an improvement in PSG data has been found [86][36]. Vitamin C improves endothelial function in OSAS patients [100][37]. Lastly, it has been found that leptin, in OSAS patients, reduces free radicals, oxidative stress, and atherosclerosis [87][38]. It is clear that antioxidant therapy could be effective in OSAS and in SNHL due to problems like aging, ototoxic drugs, and noise exposure. However, in our review, no evidence of the effectiveness of antioxidant therapy in patients affected by OSAS and SNHL combined has been found.

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